In contrast, activation of presynaptic ionotropic receptors will directly alter the electrical properties of the presynaptic terminal and cause rapid transient (millisecond time scale) changes in the probability of vesicle release (although they too can have much longer lasting effects). Binding of an ionotropic receptor will open channels in the presynaptic terminal and thereby alter the amount of transmitter released by an action potential.
Presynaptic inhibition refers to occasions when binding of presynaptic receptors leads to a decrease in release of transmitter, and it can be the result of one or more mechanisms (Fig. 6.10 ). First, opening of channels decreases membrane resistance and creates a current shunt. The shunt acts to divert the current associated with the action potential from the active zone membrane and thereby lessens the depolarization of the active zone, which results in less activation of Ca++ channels, less Ca++ entry, and less release of transmitter. A second mechanism is the change in membrane potential caused by the opening of presynaptic •Fig. 6.10 Presynapticinhibition.Activeregenerationofactionpotentialsinaxon2endsatthelastnode.Theactionpotentialisthenpassivelyconductedintotheterminal.Axon1makesanaxoaxonicsynapsewithaxon2.Activationofthissynapsereducesconductionoftheactionpotentialinaxon2totheactivezoneofitssynapticterminalbymechanismsdescribedinthetext.Thisreducestheopeningofvoltage-gatedCa++ channelsandthereforereleaseofneurotransmitter.
ionotropic channels. If a small depolarization is the result, there will be inactivation of voltage-gated Na+ channels and thereby lessening of the action potential–associated current and transmitter release. Presynaptic γ-aminobutyric acid A receptors (GABAA) occur in the spinal cord and mediate presynaptic inhibition by these mechanisms. They control Cl− channels. Generally, opening of Cl− channels generates a hyperpolarization. However, in the presynaptic terminal, the [Cl−] gradient is such that Cl− flows out of the cell and generates a small depolarization. This depolarization is small enough that it does not cause significant opening of voltage-gated Ca++ channels; otherwise, it would increase release of transmitter (presynaptic facilitation). In fact, there are other receptors that control cation channels and create large depolarizations, thereby increasing the release of transmitter. In addition, presynaptic nicotinic acetylcholine receptors control a cation channel that is permeable to Ca++ . By allowing additional entry of Ca++ , these receptors increase the release of transmitter from the terminal.
Repetitive stimulation of certain synapses in the brain can also produce more persistent changes in the efficacy of transmission at these synapses, a process called long-term potentiation or long-term depression. Such changes can persist for days to weeks and are believed to be involved in the storage of memories.